Project Summary/Abstract While the ?response to injury? associated with pathologic vascular damage has been described as the initiator of vascular graft failure, there is very little information about the molecular mediator of this process. We propose that ATP released during surgical harvest of human saphenous vein activates purinergic receptors (P2X7R) leading to a cascade of events that promulgate and potentiate the response to injury. Understanding the role of ATP and P2X7R pathway activation in response to vascular injury will lead to specific modalities to prevent and treat the injury that occurs during surgical harvest of HSV. This work will also provide new insights in vascular biology with potential extensions to other applications such as vascular injury during angioplasty, transplantation, and trauma.